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1.
ESMO Open ; 9(6): 103472, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38833972

RESUMO

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Mutação , Fatores de Transcrição , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Proteínas Cromossômicas não Histona/genética , Idoso , Proteína SMARCB1/genética , Adulto , Prognóstico , China , DNA Helicases , Proteínas de Ligação a DNA , Proteínas Nucleares
2.
Ann Oncol ; 35(2): 190-199, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37872020

RESUMO

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Sunitinibe/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Zhonghua Yi Xue Za Zhi ; 103(37): 2959-2963, 2023 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-37752056

RESUMO

Objective: To evaluate the efficacy and safety of an improved overlength biliary stent in the treatment of bile duct stricture. Methods: Prospective randomized controlled study. Patients with bile duct stricture in Peking University International Hospital from February 2016 to June 2021 were randomly divided into the conventional plastic biliary stents (CPBS) group and the improved overlength biliary stents (IOBS) group by envelope random method. CPBS or IOBS were placed after endoscopic retrograde cholangiopancreatography (ERCP) breast catheterization was successfully conducted and the stenosis length was determined by angiography. The incidence of postoperative complications, median patency time of postoperative stent and reoperation rate within 6 months were compared between the two groups, Kaplan-Meier method was used to draw the survival curve, and log-rank test was conducted to evaluate the safety and efficacy of IOBS in the treatment of bile duct stricture. Results: A total of 90 patients were included. There were 45 patients in IOBS group, including 28 males and 17 females, aged (67.2±11.7) years. There were 45 patients in CPBS group, including 26 males and 19 females, aged (64.6±14.4) years. The patients in the both groups were balanced and comparable. There were no significant differences in success rate of operation, operation time, hospitalization time, operation cost and prospective complication rate between the two groups (all P>0.05). There were no significant differences in the changes of liver function index before and 72 hours after operation between the two groups (both P>0.05). The median patency time of stents in IOBS group was longer than that in CPBS group [M(Q1, Q3), 201(155,246) vs 109(55,167) d, P=0.002].The IOBS group had lower reoperation rate than the CPBS group within 6 months [46.2% (18/39) vs 78.9%(30/38), P=0.003]. Conclusion: IOBS has good safety in the treatment of bile duct stricture and the clinical efficacy is superior to CPBS.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Colestase , Feminino , Masculino , Humanos , Constrição Patológica , Estudos Prospectivos , Colangiopancreatografia Retrógrada Endoscópica
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(6): 1178-1184, 2022 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-36533352

RESUMO

OBJECTIVE: To distinguish clinical features, safety and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) in patients after bilioenteric anstomosis based on retrospectively analyzed clinical data and endoscopy procedures. METHODS: Data extracted from patients after bilioenteric anstomosis due to biliary disease treated with ERCP from January 2005 to December 2021 in the Department of Gastroenterology, Peking University Third Hospital were retrospectively analyzed. Clinical data and endoscopic pictures were reevaluated and analyzed. The patients were divided into three groups, including the patients with choledochoduodenostomy (CDD), Roux-en-Y hepaticojejunostomy (RYHJ) and Whipple. Differences between ERCP success and failure were conducted. RESULTS: In the study, 89 cases with 132 ERCP procedures were involved, 9-80 years old, median 57 years old, containing 4 CDD, 30 RYHJ, 54 Whipple and 1 bile duct ileocecal anastomosis patients; The time between ERCP and surgery were 30 (1-40), 2.75 (0.5-14), 2 (0.3-19), and 10 years, respectively; The time between surgery and symptom were 240 (3-360), 12 (1-156), 22 (0-216), and 60 months, respectively. Fifty percent of CDD could succeed only under local anaesthesia, RYHJ (96.7%) and Whipple (100.0%) needed under general anaesthesia (P < 0.001). Successful first entry rates of CDD, RYHJ and Whipple were 100.0%, 40.0% and 77.8%, respectively. After changing the endoscopy type, successful entry rate could increase to 43.3% of RYHJ and 83.3% of Whipple. The successful entry rate of different anastomotic methods was significant (P < 0.001). The cannulation success rates of CDD, RYHJ and Whipple were 100.0%, 53.8% and 86.7% respectively, with significant difference between the groups (P=0.031). ERCP success rates of CDD, RYHJ and Whipple were 100.0%, 33.3% and 78.8% respectively, with significant difference between the groups (P < 0.001). Complications were found in 23.9% (21/88) patients, including infection (14.8%), pancreatitis (9.2%), bleeding (3.4%), and perforation (2.3%) ranked by incidence. Causes of ERCP in post bilioenteric anstomosis were anastomotic stenosis (50.0%, benign 39.3%, malignant 10.7%), choledocholithiasis (37.5%) and reflux cholangitis (12.5%). Anastomotic method was the only predicting factor of ERCP success in patients after bilioenteric anstomosis (OR=7, 95%CI: 2.591-18.912, P < 0.001). CONCLUSION: ERCP in post bilioenteric anstomosis patients with gastrointestinal reconstruction need general anaesthe-sia, with good safety and efficiency. The successful rate of RYHJ was significantly lower than Whipple. Anastomotic method was the only predicting factor of ERCP success.


Assuntos
Anastomose em-Y de Roux , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Anastomose em-Y de Roux/efeitos adversos , Anastomose em-Y de Roux/métodos , Estudos Retrospectivos , Intestino Delgado , Anastomose Cirúrgica
7.
Zhonghua Er Ke Za Zhi ; 60(12): 1322-1326, 2022 Dec 02.
Artigo em Chinês | MEDLINE | ID: mdl-36444438

RESUMO

Objective: To investigate the clinical characteristics and treatment of pancreatic pseudocyst after pegaspargase treatment in children. Methods: The clinical data of 6 children with pancreatic pseudocyst after pegaspargase treatment in the Department of Pediatrics in Peking University Third Hospital from July 2018 to February 2021 were analyzed retrospectively. Results: There were 4 males and 2 females, and their age of onset was 9.5 (5.8, 13.0) years. The total number of pegaspargase applications was 2.5 (2.0, 3.5) times. The course from the last dose of pegaspargase to the onset of pancreatitis was 11.0 (9.0, 17.2) days, and 42.5 (35.0, 129.5) days from the onset of pancreatitis to the diagnosis of pancreatic pseudocyst. Abdominal pain was the most prominent manifestation of pancreatitis (6/6). All of the 6 children were asymptomatic when pancreatic pseudocyst was noted, and were treated conservatively at first, but one case later developed intermittent abdominal distension or nausea after eating. All the cases had pancreatic pseudocyst enlargement during the conservative treatment. Three children were treated with endoscopic ultrasound-guided transgastric drainage, and the cyst disappeared from 10 days to 4 months after the operation. The other 3 children received endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage, but one of them turned to surgery due to pancreatic duct stricture, and in the rest 2 children the cyst disappeared at 1 and 3 months after operation respectively. Regarding safety issues, 1 child who received ERCP-guided transpapillary drainage had acute postoperative pancreatitis, which were improved after treatment, and the other 5 had no complications. Conclusions: Pancreatic pseudocyst after pegaspargase chemotherapy can be asymptomatic in the early stage, and should be diagnosed with a history of pegaspargase treatment and timely imaging examination. Conservative treatment is the first choice for asymptomatic pseudocyst. When the pseudocyst enlarges, different endoscopic drainage treatments are required according to whether the pseudocyst is connected with the main pancreatic duct.


Assuntos
Asparaginase , Pancreatite , Feminino , Masculino , Humanos , Criança , Estudos Retrospectivos , Polietilenoglicóis/efeitos adversos
9.
Zhonghua Nei Ke Za Zhi ; 61(8): 916-920, 2022 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-35922216

RESUMO

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.


Assuntos
Isquemia Encefálica , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Pressão Sanguínea , Isquemia Encefálica/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Piperazinas , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
11.
Eur Cell Mater ; 43: 252-266, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35652679

RESUMO

Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.


Assuntos
Osteogênese , Polietilenotereftalatos , Animais , Fosfatos de Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Colágeno/metabolismo , Colágeno/farmacologia , Polietilenotereftalatos/farmacologia , Coelhos , Ratos , Microtomografia por Raio-X
12.
Phys Rev Lett ; 128(8): 085003, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35275672

RESUMO

High-ß_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-ß_{θe} regime.

13.
Zhonghua Gan Zang Bing Za Zhi ; 30(10): 1100-1106, 2022 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-36727235

RESUMO

Objective: To explore the relationship between the hepatic caudate lobe boundary and the ductal system so as to guide the identification of the anatomical relationship during liver surgery. Methods: The specific parts were observed and the liver parenchyma was removed according to 41 cadaveric liver autopsy specimens. The critical relationship between the hepatic caudate lobe and other ducts was observed to explore the reticular duct structure. Results: The plane formed by the hepatic hilar plate and Arantius ligament served as the boundary between the caudate lobe and other hepatic lobes. The caudate lobe hepatic portal vein was composed of numerous small branches from its left and right branches. The portal vein adjacent to the vena cava was mainly derived from the left branch, and to a lesser extent from the right branch. Blood was drained straight from the caudate lobe vein into the inferior vena cava via the short hepatic vein. There were three or four bile duct branches in the caudate lobe. The main source of arterial blood flow were the left and right branches of the hepatic artery. An avascular zone of loose connective tissue was found between the caudate lobe and the retrohepatic inferior vena cava. Conclusion: The hepatic caudate lobe is an independent lobe. During hepatic caudate lobe surgery, the plane formed by the hepatic hilar plate and Arantius ligament can serve as the boundary between the caudate lobe and other hepatic lobes and be used for anatomical site identification. The duct system of the caudate lobe's is complicated, but it also has its own distinct regularity.


Assuntos
Artéria Hepática , Fígado , Humanos , Fígado/irrigação sanguínea , Ductos Biliares , Veia Porta , Veias Hepáticas , Hepatectomia
15.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(10): 1616-1622, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-33297617

RESUMO

Objective: To analyzes epidemiological characteristics of COVID-19 and provide evidence for adjustment for COVID-19 prevention and control strategies. Methods: The data of COVID-19 cases in Wuchang district reported as of 19 March, 2020 were obtained from National Notifiable Disease Report System of Chinese Disease Prevention and Control Information System. The software's of Excel 2010, SPSSS 22.0, Arc GIS10.2 and Joinpoint regression program 4.8.0.0 were used for statistical analysis. Results: A total of 7547 COVID-19 cases had been reported as of 19 March, 2020 in Wuchang district, including 5 448 confirmed cases (72.19%), 2009 clinical diagnosed cases (26.62%) and 90 asymptomatic cases case (1.19%). The age of the cases was (56.65±16.25) years and age ranged from 2 days to 105 years among confirmed cases, 2634 were males (48.35%) and 2814 were females (51.65%), 2 492 were retirees (45.74%). A total of 545 health workers were infected with SARS-CoV-2 (7.22% of all cases) including 365 confirmed cases and 5 cases have died. A total of 430 cases of death were reported with case fatality rate of 7.89% (430/5 448), case fatality rate of males (10.9%, 266/2 634) was higher than that of females (5.82%, 164/2 814). The first phase of epidemic peak was from January 24 to January 26, the second phase of epidemic peak was from February 1 to February 5 and there was no one of new confirmed case in one day for the first time on March 18. The first four Streets with the highest incidence rates of confirmed cases were Huanghelou Street (1 043.77/100 000), Ziyang Street (627.97/100 000), Yangyuan Street (503.67/100 000) and Shuiguohu Street (486.02/100 000). Compared with females, aged ≤50 years and mild cases of clinical classification respectively, males (RR=0.690, 95%CI: 0.322-1.478), aged >50 years (RR=11.745, 95%CI: 6.878-20.058), severe cases (RR=2.317, 95%CI: 1.789-3.000) and critical cases of clinical classification (RR=10.794, 95%CI: 7.997-14.569), and gender time-dependent covariate (RR=1.392, 95%CI: 1.053-1.840) were major influencing factors of prognosis of COVID-19 confirmed cases. Conclusions: The gender, ages and occupation of distribution were wide among COVID-19 cases in Wuchang district. Males, aged >50 years, severe cases and critical cases of clinical classification were influencing factors of prognosis of COVID-19 confirmed cases. The standardized management of discharged cases, asymptomatic infected cases and close contact persons were main measures to reduce incidence rates of COVID-19 cases.


Assuntos
COVID-19/epidemiologia , Pandemias , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Criança , Pré-Escolar , China/epidemiologia , Feminino , Pessoal de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Ocupações , Fatores Sexuais , Adulto Jovem
16.
Braz. j. biol ; 80(4): 948-956, Oct.-Dec. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1142528

RESUMO

Abstract Mucosal epithelial cells act as the first immunologic barrier of organisms, and contact directly with pathogens. Therefore, hosts must have differential strategies to combat pathogens efficiently. Reactive oxygen species (ROS), as a kind of oxidizing agents, participates in the early stage of killing pathogens quickly. Recent reports have revealed that dual oxidase (DUOX) plays a key role in mucosal immunity. And the DUOX is a transmembrane protein which produces ROS as their primary enzymatic products. This process is an important pattern for eliminating pathogens. In this review, we highlight the DUOX immunologic functions in the respiratory and digestive tract of vertebrates.


Resumo As células epiteliais da mucosa atuam como a primeira barreira imunológica dos organismos e entram em contato direto com os patógenos. Portanto, os hospedeiros devem ter estratégias diferenciadas para combater os patógenos de forma eficiente. Trabalhos recentes revelaram que a oxidase dupla (DUOX) desempenha um papel fundamental para a imunidade da mucosa. A DUOX é uma proteína transmembrana geradora de espécies reativas de oxigênio (EROs) como seus principais produtos enzimáticos. Nesta revisão, apresentaremos as funções imunológicas da DUOX no trato respiratório e digestivo dos vertebrados.


Assuntos
Animais , Vertebrados , NADPH Oxidases , Espécies Reativas de Oxigênio , Oxidases Duais
17.
Eur Rev Med Pharmacol Sci ; 24(12): 6551-6560, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633342

RESUMO

OBJECTIVE: As a new LncRNA, anti-differentiated non-coding RNA (DANCR) plays an important role in tumorigenesis and development, and its molecular mechanism in osteosarcoma is unclear. In this study, by investigating osteosarcoma tissue and cells, we explored the molecular mechanism by which lncRNA DANCR regulates the occurrence and development of osteosarcoma by targeting the miR-149 / MSI2 axis. PATIENTS AND METHODS: In this study, osteosarcoma tissues and adjacent tissues in 109 patients were collected, and the relative expression of DANCR was detected by qPCR. The correlation between DANCR expression and clinical classification was statistically analyzed. In order to explore the potential molecular mechanism of DANCR related to tumor migration and invasion, an overexpression and silencing test was performed on the osteosarcoma cell line Saos-2, and then qPCR method was used to test the expression of miR149, and cell scratch test was used to detect invasion after DANCR silencing and miR149 overexpression. Transwell assay was used to detect the invasion after DANCR silencing and miR149 overexpression. Finally, Western blot was used to verify the expression of MSI2 protein after overexpression and silencing of miR-149. RESULTS: DANCR was significantly up-regulated in both osteosarcoma tissue and cells. The high expression of DANCR was significantly positively correlated with tissue typing and advanced TNM stage. DANCR can significantly reduce the migration and invasion of osteosarcoma cells. miRNA overexpression significantly reduced osteosarcoma cell migration and invasion. When miR-149 was overexpressed, MSI2 protein expression was significantly down-regulated. When miR-149 was silenced, MSI2 protein was significantly up-regulated. CONCLUSIONS: LncRNA DANCR plays an important regulatory role in the occurrence and development of osteosarcoma. It may be used as a potential target in the treatment of osteosarcoma in the future, by targeting the miR-149/MSI2 axis to regulate the occurrence and development of osteosarcoma.


Assuntos
Neoplasias Ósseas/metabolismo , Movimento Celular/fisiologia , MicroRNAs/biossíntese , Osteossarcoma/metabolismo , RNA Longo não Codificante/biossíntese , Proteínas de Ligação a RNA/biossíntese , Adulto , Neoplasias Ósseas/patologia , Feminino , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , Proteínas de Ligação a RNA/antagonistas & inibidores , Adulto Jovem
18.
Zhonghua Yi Xue Za Zhi ; 100(22): 1699-1703, 2020 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-32536088

RESUMO

Objective: To investigate the novel genetic cause associated with hypospadias and the strategy for preventing offspring genetic defects in these patients. Methods: In March 2019, a patient with gonadal dysplasia (hypospadias associated with cryptorchidism) was referred to Shanghai General Hospital. His secondary sex characters, level of sex hormones and the development of male reproductive system was assessed through physical examination, sex hormone examination, male reproductive system B-ultrasound and computed tomography (CT). Whole-exome sequencing (WES) was preformed to investigate the pathogenic genetic variations associated with hypospadias and cryptorchidism. Also, Sanger sequencing was conducted to verify the WES results in the pedigree. Semen analysis was used to assess the fertility of the proband and the SRD5A2 gene analysis of his spouse was performed to assess the risk of genetic defects in the offspring. Results: The patient suffered from gonadal dysplasia (hypospadias associated with cryptorchidism). Physical examination showed an inverted triangular distribution of pubic hair, small penis and the volume of the testis was 8 ml. Sex hormone examination revealed the level of FSH, LH, Pituitary prolactin (PRL), estrogen (E(2)), testosterone (T), and sex hormone-binding globulin (SHBG) was 25.81 U/L, 10.84 U/L, 21.09 µg/L, 153 pmol/L, 16.95 nmol/L, and 36.15 nmol/L respectively. B-ultrasound and computed tomography (CT) showed left inguinal testis. Also, semen analysis illustrated that the volume was 0.05 ml and sperm concentration<2×10(6)/ml, suggesting oligospermia in this case. WES sequencing and Sanger sequencing showed compound heterozygous LoF mutations in SRD5A2 [NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] in this patient. And there were no pathogenic genetic variations of SRD5A2 in the spouse. Conclusion: Novel compound heterozygous LoF mutations in SRD5A2[NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] may be the primary cause of disorders of sex development.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Criptorquidismo , Transtornos do Desenvolvimento Sexual , Proteínas de Membrana/genética , China , Transtornos do Desenvolvimento Sexual/genética , Humanos , Masculino , Mutação , Globulina de Ligação a Hormônio Sexual , Testosterona
19.
Zhonghua Yi Shi Za Zhi ; 50(1): 39-42, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32564536

RESUMO

Euibangyoochui compiled by the Korean government was finished in 1445. This book is a collection of Korean medicine. It quoted some contents from Compendium of Effective Prescriptions for Women. This paper use the photocopy of the Japanese edition of the first year of Fumihisa(1861)printed in Korea as the master copy of Euibangyoochui, the microfilm of the edition of Qin You Shu Tang in Yuan Dynasty as the master copy of Compendium of Effective Prescriptions for Women, in order to compare the content of Compendium of Effective Prescriptions for Women quoted in Euibangyoochui. There are 42 direct citations from Compendium of Effective Prescriptions for Women in Euibangyoochui, 41 of which are in gynecology, and 1 of which is in pediatrics. The indirect citations are divided into two types: single line big characters and double line small characters, no obvious rules. Meanwhile, it is found that the direct quotation is adjusted according to the style and content, and the differences between the quotation and the yuan edition are mostly small, which can be corrected and supplemented each other, it is of great reference value for collating the Compendium of Effective Prescriptions for Women.


Assuntos
Livros/história , Medicina Tradicional Coreana , Filologia , Feminino , Ginecologia , História do Século XV , Humanos , Prescrições , República da Coreia
20.
Zhonghua Yi Xue Za Zhi ; 100(18): 1432-1436, 2020 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-32392996

RESUMO

Objective: To study the efficacy and safety of low-intensity pulsed ultrasound (LIPUS) at different intervals by mechanical force in treating erectile dysfunction (ED). Method: Forty patients with mild to moderate ED were randomized in a 1∶1 ratio to receive 16-treatment sessions of LIPUS in group A and group B, applied 3 times per week and 2 times per week, respectively. End-point assessments were made at 8th week after treatment. Efficacy were evaluated using International Index of Erectile Function-Erectile Function domain score (IIEF-EF), Erectile Hardness Score (EHS), Self-Esteem and Relationship Questionnaire (SEAR), Sexual Encounter Profile (SEP), Global Assessment Question (GAQ), and pain were assessed by Visual Analogue Score (VAS).Treatment response was confirmed by a minimal clinically importance difference (MCID) at 8th week. Results: Compared with baseline, IIEF-EF score [(17.1±5.48 vs 23.4±3.75, P<0.05) and (18.9±4.34 vs 24.1±4.32, P<0.05)], proportion of EHS 4 [(0 vs 40%, P<0.05) and (16.7% vs 55.6%, P<0.05)], and Overall Relationship score [(50.6 vs 67.5, P<0.05) and (44.4 vs 70.1, P<0.05)] were significantly improved at 8th week in two groups, respectively. Compared with baseline, the positive responses to SEP-3 increased significantly at 8th week in two groups (50.0% vs 80.0%,P<0.05) and (44.4% vs 88.9%, P<0.05), respectively. The positive responses to GAQ-2 were 90.0% and 88.9% at 8th week in two groups, respectively. There were no significant differences in IIEF-EF, EHS, SEAR, SEP and GAQ at 8th week between two groups. There was no significant difference in treatment response using MCID between two groups at end-point (80.5% vs 77.5%). The treatment duration for full sessions were 2.5 weeks less in group A than group B. No adverse effects were reported in all cases. Conclusion: LIPUS at two different intervals is effective and safe for mild to moderate ED, and the regimen at 3 times per week can achieve quite good effect in relatively short duration,while the long-term effects is still be clarified in further study.


Assuntos
Disfunção Erétil , Ondas Ultrassônicas , Método Duplo-Cego , Disfunção Erétil/terapia , Humanos , Masculino , Ereção Peniana , Resultado do Tratamento , Terapia por Ultrassom
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